Is Chondroitin Sulfate a Safe and Effective Option for Patients with Osteoarthritis?

Background: Osteoarthritis (OA) is the most common musculoskeletal disease affecting humans and a major cause of pain, loss of function, and disability among patients. Acetaminophen, a first line-agent for treating OA is often well-tolerated but has limited effectiveness in patients with more advanced disease. Other traditional therapy options such as non-steroidal anti-inflammatory drugs (NSAIDs) introduce several safety concerns, drug-drug interactions and comorbidity complications. With these limitations, patients may turn to alternative therapies such as glucosamine and chondroitin making it important for pharmacists to be familiar with these options allowing them to advise patients appropriately about their use. The most recent clinical practice guidelines from the American College of Rheumatology in 2012 recommend against the use of chondroitin sulfate supplements due to a lack of complete evidence. Newer studies have been published suggesting chondroitin sulfate be re-examined for its use in OA.

Evidence: A randomized, double-blind, placebo-control trial of 604 patients demonstrated that pharmaceutical grade chondroitin sulfate 800 mg/day was as effective in reducing pain and improving function as celecoxib 200 mg/day and was superior to placebo in symptomatic knee OA given over a 6-month period. The visual analog scale (VAS) was used to measure pain and Lequesne’s index (LI) was used as a composite assessment of pain and function. Compared to placebo, both treatments were superior as measured by the LI but celecoxib showed a significant difference at day 30 while chondroitin sulfate did not have this effect until day 91. Significant differences in the VAS were demonstrated in both treatment groups but not until day 182 for either. Minimal clinically important improvement was analyzed as a secondary outcome and did not reach statistical significance in either group as compared to placebo. No significant adverse effects were observed in any group, though abdominal discomfort occurred more frequently in celecoxib than the others.

A Cochrane review of chondroitin sulfate analyzed 4,962 patients with osteoarthritis treated with chondroitin sulfate taken alone or with glucosamine sulfate compared to 4,148 patients treated with placebo or an active control across 43 randomized controlled trials. Only 4 trials examined chondroitin sulfate dosing of less than 800 mg/day. Trial durations varied from 1 month to 3 years and participants in the treatment groups achieved statistically significant and clinically meaningful improvements in their pain scores in studies less than 6 months with an absolute risk difference of 10% (95% CI, 15% - 6%) lower than the placebo group. Trials looking at doses of < 800 mg/day failed to demonstrate statistical significance though the number of patients analyzed was very low. Other outcomes such as physical function, stiffness, and grip strength did not achieve significant differences. Studies had a high level of heterogeneity, high level of bias, and overall level of evidence was low.

Discussion: Despite new studies making exciting claims about the use of chondroitin sulfate, the evidence continues to be ambiguous. Though statistical significance was demonstrated in the study comparing chondroitin to celecoxib, the chondroitin did fail to reach the threshold for clinical significance set by the study design. A significant difference is seen in the Cochrane review in pain scores for shorter durations (6 months or less) of treatment. The studies overall had a high level of variability and bias introducing greater potential for confounding factors such as concurrent glucosamine and breakthrough medication use. Additionally, this review only found significant results in pain scores but other factors such as physical function showed no difference leaving clinical implications inconclusive. No significant adverse effects or safety concerns were noted among any of the reviewed evidence.

Clinical Impact: The use of chondroitin sulfate is not recommended based on current clinical practice guidelines. However, if a patient is inquiring about the use of these supplements due to contraindications or lack of success with recommended pharmacologic therapies the risks of doing so are low. Patients should be educated about realistic expectations regarding the use of these products and understand that it may take months to see a benefit. The effects in using it beyond 6 months are not yet fully understood.

Hochberg MC, Altman RD, April KT, et al. American college of rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012;64(4):465-474.